Heparin

Today's med: Heparin and UFH (Unfractionated Heparin) 

(brand names: Hep-Lock, HepFlush-10 )

Drug Class: Anticoagulant

Other Drugs in this class: Dalteparin sodium, Bivalirudin, Argatroban, 

Lepirudin,Heparin Sodium, Heparin/Dextrose

Indications: Prophylaxis and treatment of thromboembolic disorders; as an anticoagulant for extracorporeal and dialysis procedures

Note: Heparin lock flush solution is intended only to maintain patency of I.V. devices and is not to be used for systemic anticoagulant therapy.

Use: Unlabeled

ST-elevation myocardial infarction (STEMI) as an adjunct to thrombolysis; unstable angina/non-STEMI (UA/NSTEMI); anticoagulant used during percutaneous coronary intervention (PCI)

Action: Potentiates the action of antithrombin III and thereby inactivates thrombin (as well as activated coagulation factors IX, X, XI, XII, and plasmin) and prevents the conversion of fibrinogen to fibrin; heparin also stimulates release of lipoprotein lipase (lipoprotein lipase hydrolyzes triglycerides to glycerol and free fatty acids)

Contraindications: Hypersensitivity to heparin or any component of the formulation (unless a life-threatening situation necessitates use and use of an alternative anticoagulant is not possible); severe thrombocytopenia; uncontrolled active bleeding except when due to disseminated intravascular coagulation (DIC); not for use when appropriate blood coagulation tests cannot be obtained at appropriate intervals (applies to full-dose heparin only) Note: Some products contain benzyl alcohol as a preservative; their use in neonates, infants, or pregnant or nursing mothers is contraindicated by some manufacturers.

Adverse Effects: Frequency not defined.

Cardiovascular: Allergic vasospastic reaction (possibly related to thrombosis), chest pain, hemorrhagic shock, shock, thrombosis

Central nervous system: Chills, fever, headache

Dermatologic: Alopecia (delayed, transient), bruising (unexplained), cutaneous necrosis, dysesthesia pedis, erythematous plaques (case reports), eczema, urticaria, purpura

Endocrine & metabolic: Adrenal hemorrhage, hyperkalemia (suppression of aldosterone synthesis), ovarian hemorrhage, rebound hyperlipidemia on discontinuation

Gastrointestinal: Constipation, hematemesis, nausea, tarry stools, vomiting

Genitourinary: Frequent or persistent erection

Hematologic: Bleeding from gums, epistaxis, hemorrhage, ovarian hemorrhage, retroperitoneal hemorrhage, thrombocytopenia (see note)

Hepatic: Liver enzymes increased

Local: Irritation, erythema, pain, hematoma, and ulceration have been rarely reported with deep SubQ injections; I.M. injection (not recommended) is associated with a high incidence of these effects

Neuromuscular & skeletal: Peripheral neuropathy, osteoporosis (chronic therapy effect)

Ocular: Conjunctivitis (allergic reaction), lacrimation

Renal: Hematuria

Respiratory: Asthma, bronchospasm (case reports), hemoptysis, pulmonary hemorrhage, rhinitis

Miscellaneous: Allergic reactions, anaphylactoid reactions, heparin resistance, hypersensitivity (including chills, fever, and urticaria)

Lab Test Interferences: 

Increased thyroxine (competitive protein binding methods); increased PT.  

Aprotinin significantly increases aPTT and celite Activated Clotting Time (ACT) which may not reflect the actual degree of anticoagulation by heparin. Kaolin-based ACTs are not affected by aprotinin to the same degree as celite ACTs. While institutional protocols may vary, a minimal celite ACT of 750 seconds or kaolin-ACT of 480 seconds is recommended in the presence of aprotinin. Consult the manufacturer’s information on specific ACT test interpretation in the presence of aprotinin.

Standard Dosing: Note: Many concentrations of heparin are available ranging from 1 unit/mL to 20,000 units/mL. Carefully examine each prefilled syringe or vial prior to use ensuring that the correct concentration is chosen. Heparin lock flush solution is intended only to maintain patency of I.V. devices and is not to be used for anticoagulant therapy.

Children >1 year:

Prophylaxis for cardiac catheterization (arterial approach): I.V.: Bolus: 100 units/kg (Freed, 1974; Monagle, 2012)

Systemic heparinization:

Intermittent I.V.: Initial: 50-100 units/kg, then 50-100 units/kg every 4 hours (Note: Continuous I.V. infusion is preferred)

I.V. infusion: Initial loading dose: 75 units/kg given over 10 minutes, then initial maintenance dose: 20 units/kg/hour; adjust dose to maintain aPTT of 60-85 seconds (assuming this reflects an antifactor Xa level of 0.35-0.7 units/mL); see table.

Pediatric Protocol For Systemic Heparin Adjustment

To be used after initial loading dose and maintenance I.V. infusion dose (see usual dosage listed above) to maintain aPTT of 60-85 seconds (assuming this reflects antifactor Xa level of 0.35-0.7 units/mL).

Obtain blood for aPTT 4 hours after heparin loading dose and 4 hours after every infusion rate change.

Obtain daily CBC and aPTT after aPTT is therapeutic.

aPTT (seconds)	Dosage Adjustment	Time to Repeat aPTT
Modified from Andrew M, et al, “Heparin Therapy in Pediatric Patients: A Prospective Cohort Study,”Pediatr Research, 1994, 35(1):78-83. Note: The aPTT range of 60-85 seconds corresponds to an anti-Xa level of 0.35-0.7 units/mL.
<50	Give 50 units/kg bolus and increase infusion rate by 10%	4 h after rate change
50-59	Increase infusion rate by 10%	4 h after rate change
60-85	Keep rate the same	Next day
86-95	Decrease infusion rate by 10%	4 h after rate change
96-120	Hold infusion for 30 minutes and decrease infusion rate by 10%	4 h after rate change
>120	Hold infusion for 60 minutes and decrease infusion rate by 15%	4 h after rate change

Table has been converted to the following text.

Suggested Dosing Adjustments:*

aPTT <50 seconds

Dosage adjustment: Give 50 units/kg bolus and increase infusion rate by 10%

Time to repeat aPTT: 4 hours after rate change

aPTT 50-59 seconds

Dosage adjustment: Increase infusion rate by 10%

Time to repeat aPTT: 4 hours after rate change

aPTT 60-85 seconds

Dosage adjustment: Keep rate the same

Time to repeat aPTT: Next day

aPTT 86-95 seconds

Dosage adjustment: Decrease infusion rate by 10%

Time to repeat aPTT: 4 hours after rate change

aPTT 96-120 seconds

Dosage adjustment: Hold infusion for 30 minutes and decrease infusion rate by 10%

Time to repeat aPTT: 4 hours after rate change

aPTT >120 seconds

Dosage adjustment: Hold infusion for 60 minutes and decrease infusion rate by 15%

Time to repeat aPTT: 4 hours after rate change

*Modified from Andrew M, et al, “Heparin Therapy in Pediatric Patients: A Prospective Cohort Study,” Pediatr Research, 1994, 35(1):78-83.

Note: The aPTT range of 60-85 seconds corresponds to an anti-Xa level of 0.35-0.7 units/mL.

Adults:

Thromboprophylaxis (low-dose heparin): SubQ: 5000 units every 8-12 hours. Note: The American College of Chest Physicians recommends a minimum of 10-14 days for patients undergoing total hip arthroplasty, total knee arthroplasty, or hip fracture surgery (Guyatt, 2012).

Intermittent I.V.: Initial: 10,000 units, then 50-70 units/kg (5000-10,000 units) every 4-6 hours

Percutaneous coronary intervention (Levine, 2011):

No prior anticoagulant therapy:

If no GPIIb/IIIa inhibitor use planned: Initial bolus of 70-100 units/kg (target ACT 250-300 seconds for HemoTec®, 300-350 seconds for Hemochron®)

or

If planning GPIIb/IIIa inhibitor use: Initial bolus of 50-70 units/kg (target ACT 200-250 seconds regardless of device)

Prior anticoagulant therapy:

If no GPIIb/IIIa inhibitor use planned: Additional heparin as needed (eg, 2000-5000 units) (target ACT 250-300 seconds for HemoTec®, 300-350 seconds for Hemochron®)

or

If planning GPIIb/IIIa inhibitor use: Additional heparin as needed (eg, 2000-5000 units) (target ACT 200-250 seconds regardless of device)

I.V. infusion (weight-based dosing per institutional nomogram recommended):

Acute coronary syndromes:

STEMI: Adjunct to fibrinolysis (full-dose alteplase, reteplase, or tenecteplase) (Antman, 2008): Initial bolus of 60 units/kg (maximum: 4000 units), then 12 units/kg/hour (maximum: 1000 units/hour) as continuous infusion. Check aPTT every 4-6 hours; adjust to target of 1.5-2 times the upper limit of control (50-70 seconds). Duration of heparin therapy depends on concurrent therapy and the specific patient risks for systemic or venous thromboembolism.

Unstable angina (UA)/non-ST-elevation myocardial infarction (NSTEMI) (Anderson, 2007): Initial bolus of 60 units/kg (maximum: 4000 units), followed by an initial infusion of 12 units/kg/hour (maximum: 1000 units/hour). Check aPTT every 4-6 hours; adjust to target of 1.5-2 times the upper limit of control (50-70 seconds). Continue for 48 hours in low risk patients managed with a conservative strategy (ie, no diagnostic angiography or PCI) (Jneid, 2012).

Treatment of venous thromboembolism: Note: Start warfarin on the first or second treatment day and continue heparin until INR is ≥2 for at least 24 hours (usually 5-7 days) (Guyatt, 2012).

DVT/PE (unlabeled dosing): I.V.: 80 units/kg (or alternatively 5000 units) I.V. push followed by continuous infusion of 18 units/kg/hour (or alternatively 1000 units/hour) (Guyatt, 2012)

or

DVT/PE (unlabeled dosing): SubQ: Unmonitored dosing regimen: Initial: 333 units/kg then 250 units/kg every 12 hours (Guyatt, 2012; Kearon, 2006)

Line flushing: When using daily flushes of heparin to maintain patency of single and double lumen central catheters, 10 units/mL is commonly used for younger infants (eg, <10 kg) while 100 units/mL is used for older infants, children, and adults. Capped PVC catheters and peripheral heparin locks require flushing more frequently (eg, every 6-8 hours). Volume of heparin flush is usually similar to volume of catheter (or slightly greater). Additional flushes should be given when stagnant blood is observed in catheter, after catheter is used for drug or blood administration, and after blood withdrawal from catheter.

Addition of heparin (0.5-3 unit/mL) to peripheral and central parenteral nutrition has not been shown to decrease catheter-related thrombosis. The final concentration of heparin used for TPN solutions may need to be decreased to 0.5 units/mL in small infants receiving larger amounts of volume in order to avoid approaching therapeutic amounts. Arterial lines are heparinized with a final concentration of 1 unit/mL.

Administration

SubQ: Inject in subcutaneous tissue only (not muscle tissue). Injection sites should be rotated (usually left and right portions of the abdomen, above iliac crest).

I.M.: Do not administer I.M. due to pain, irritation, and hematoma formation; central venous catheters must be flushed with heparin solution when newly inserted, daily (at the time of tubing change), after blood withdrawal or transfusion, and after an intermittent infusion through an injectable cap. A volume of at least 10 mL of blood should be removed and discarded from a heparinized line before blood samples are sent for coagulation testing.

Continuous I.V. infusion: Infuse via infusion pump. If preparing solution, mix thoroughly prior to administration.

Heparin lock: Inject via injection cap using positive pressure flushing technique. Heparin lock flush solution is intended only to maintain patency of I.V. devices and is not to be used for anticoagulant therapy.

Concerns related to adverse effects:

• Bleeding: Monitor patient closely for signs or symptoms of bleeding. Certain patients are at increased risk of bleeding; risk factors include subacute bacterial endocarditis; congenital or acquired bleeding disorders; active ulcerative or angiodysplastic GI diseases; continuous GI tube drainage; severe uncontrolled hypertension; history of hemorrhagic stroke; or use shortly after brain, spinal, or ophthalmologic surgery or other invasive procedures including spinal tap or spinal anesthesia; concomitant treatment with platelet inhibitors; recent GI bleeding; thrombocytopenia or platelet defects; severe liver disease; hypertensive or diabetic retinopathy; renal failure; or in patients (especially women) >60 years of age. Discontinue if bleeding occurs; severe hemorrhage or overdosage may require protamine.

• Heparin-induced thrombocytopenia (HIT): May cause thrombocytopenia; monitor platelet count closely. Patients who develop HIT may be at risk of developing a new thrombus (heparin-induced thrombocytopenia and thrombosis [HITT]). Discontinue therapy and consider alternatives if platelets are <100,000/mm³ and/or thrombosis develops. HIT or HITT may be delayed and can occur up to several weeks after discontinuation of heparin. Use with extreme caution (for a limited duration) or avoid in patients with history of HIT, especially if administered within 100 days of HIT episode (Dager, 2007; Warkentin, 2001); monitor platelet count closely.

• Heparin resistance: Dose requirements >35,000 units/24 hours to maintain a therapeutic aPTT may occur in patients with antithrombin deficiency, increased heparin clearance, elevations in heparin-binding proteins, elevations in factor VIII and/or fibrinogen; frequently encountered in patients with fever, thrombosis, thrombophlebitis, infections with thrombosing tendencies, MI, cancer, and in postsurgical patients; measurement of anticoagulant effects using antifactor Xa levels may be of benefit.

• Hyperkalemia: Monitor for hyperkalemia; can cause hyperkalemia by suppressing aldosterone production.

• Hypersensitivity reactions: May occur; only in life-threatening situations when use of an alternative anticoagulant is not possible should heparin be cautiously used in patients with a documented hypersensitivity reaction.

• Osteoporosis: May occur with prolonged use (>6 months) due to a reduction in bone mineral density.

Special populations:

• Elderly: Use with caution in patients >60 years of age, particularly women; they are also more sensitive to the dose and a higher incidence of bleeding has been reported in these patients. May require lower doses.

Dosage form specific issues:

• Benzyl alcohol: [U.S. Boxed Warning]: Some products contain benzyl alcohol as a preservative; use of these products is contraindicated in neonates. In neonates, large amounts of benzyl alcohol (>100 mg/kg/day) have been associated with fatal toxicity (gasping syndrome). Use in neonates, infants, or pregnant or nursing mothers is contraindicated by some manufacturers; the use of preservative-free heparin is, therefore, recommended in these populations.

• Sulfites: Some preparations contain sulfite which may cause allergic reactions.

Other warnings/precautions:

• Fatal medications errors: Many concentrations of heparin are available ranging from 1 unit/mL to 20,000 units/mL. Clinicians must carefully examine each prefilled syringe or vial prior to use ensuring that the correct concentration is chosen; fatal hemorrhages have occurred related to heparin overdose especially in pediatric patients.

Drug interactions: http://www.drugs.com/drug-interactions/heparin.html

A total of 272 drugs (1005 brand and generic names) are known to interact with heparin.

• 40 major drug interactions (98 brand and generic names)
• 204 moderate drug interactions (835 brand and generic names)
• 28 minor drug interactions (72 brand and generic names)

Show all medications in the database that may interact with heparin.

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Consider therapy modification

Omega-3 Fatty Acids: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Vitamin E: May enhance the anticoagulant effect of Anticoagulants. Vitamin E may also increase the overall risk for bleeding. Monitor therapy

Fractionated heparin is manufactured from unfractionated heparin (UFH) to produce a much smaller-sized compound that has similar properties in terms of prevention of clotting, but requires more preparation.  Unfractionated heparin costs far less than fractionated heparin because of the added processing required to produce it.  Both forms of heparin have been shown to be equally effective for clot prevention. However, fractionated heparin can be given less frequently (once daily) and can also cause less bleeding in patients. An advantage to using fractionated heparin is that is does not require the constant blood monitoring in the laboratory (aPTT/PT/INR) that unfractionated heparin does.

Read more: http://www.ehow.com/facts_5985947_fractionated-vs_-unfractionated-heparin.html#ixzz2k6cgHHVW